Monascus has been used in Chinese fermented foods for thousands of years. Various pharmaceutical uses of Monascus fermented products have also been recorded. In addition to traditional use in production of pigments, red yeast rice fermented with Monascus spp. has recently been used to produce bioactive metabolites such as γ-aminobutyric acid (GABA) used as an anti-hypertension agent (see Tsuji, K., et al., 1992, “Effects of two kinds of Koji on blood pressure in spontaneously hypertensive rats.” Nippon. Nogeikagaku Kaishi., 66: 1241-1246), polyketides monacolin K used as a cholesterol-lowering drug (see Endo, A., 1979, “Monacolin K, a new hypocholesterolemic agent produced by a Monascus species.” J. Antbiot., 32: 852-854; Endo, A., 1985, “Compactin (ML-236B) and related compounds as potential cholesterol-lowering agents that inhibit HMG-CoA reductase.” J. Med. Chem., 28: 401-405; and Martinokova, L., et al., 1995, “Biological activity of polyketide pigments produced by the fungus Monascus.” J. Appl. Bacteriol., 79: 609-616), and demerumic acid used as an anti-oxidant (see Juzlová, P., et al., 1996, “Secondary Metabolites of the Fungus Monascus: a Review.” Journal of Industrial Microbiology, 16: 163-170). Furthermore, red yeast rice fermented with Monascus spp. has been reported to inhibit tumor growth, protect liver function, inhibit adipocyte differentiation, resist fatigue, improve immune function, lower hyperlipidemia, and lower blood glucose, and is widely consumed as a health food and drug (see Loret, M.-O. & Morel, S., 2010, “Isolation and structural characterization of two new metabolites from Monascus.” J Agric Food Chem., 58: 1800-1803).
A randomized double-blind controlled trial conducted in the University of California, Los Angeles Medical Center (see Heber D., et al., 1999, “Cholesterol-lowering effects of a proprietary Chinese red-yeastrice dietary supplement.” Am J Clin Nutr., 69: 231-236) found that LDL, total cholesterol, and triglycerides in subjects suffering from hyperlipidemia decreased by 22%, 17%, and 11%, respectively, in the experimental group treated with the red yeast rice fermented with Monascus spp., while those in the control group maintained the original values. The study also confirmed that red yeast rice fermented with Monascus spp. is superior to conventional lipid-lowering drugs because it does not adversely affect liver function or cause other side effects. According to a report by the Shanghai First People's Hospital regarding the effect of red yeast rice fermented with Monascus spp. as compared with Pravastatin in treating hyperlipidemia (see Yang H T., et al., 1997, “A comparative Study of Xuezhikang and Mevalotin in treatment of Essential Hyperlipidemia.” Chinese Journal of New Drugs, 6: 265-268), total cholesterol, low density lipoprotein cholesterol and Apo B decreased by 26.59% vs 18.92%, 33.32% vs 24.24%, and 18.42% vs 8.89%, respectively, showing that the red yeast rice fermented with Monascus spp. has a significantly superior effect. A study conducted at the Chinese Academy of Medical Sciences Deng Sisuo Hospital (see Lin, Feng., 1992, “Evolution of research and development of Monascus.” Scientific agriculture, 40: 193-198) also confirmed that red yeast rice fermented with Monascus spp. is effective in treatment of subjects with high cholesterol. Red yeast rice fermented with Monascus spp. has since become commercialized as a lipid-lowering drug and for prevention of coronary heart disease.
In addition, the blood-glucose-lowering effect of red yeast rice fermented with Monascus spp. was reported in 1988 (see Tamada Hideaki, 1988, “Red yeast rice application of a variety of seasonings.” Food and Science, July: 96-99). The blood glucose level of rabbits fed red yeast rice fermented with Monascus spp. was reduced by about 30%. Shi, Y. and Pan, T., J. (“Anti-diabetic effects of Monascus purpureus NTU 568 fermented products on streptozotocin-induced diabetic rats.” J. Agric. Food Chem., 2010, 58(13): 7634-7640) report that red yeast rice fermented with Monascus spp. has anti-diabetic effects.
Modulating lipid metabolism is one strategy for the treatment of metabolic syndrome. Thiazolidinediones (TZDs) are type 2 diabetes drugs developed in the early 1980s. Studies on the mechanisms of TZDs showed that they increase insulin sensitivity by activating PPARγ. One of the characteristic effects of activating PPARγ is increasing differentiation of adipocytes. Increasing adipocyte differentiation has therefore become a popular method for screening agents that have potential in activating PPARγ and decreasing insulin resistance.
However, the prior arts do not disclose which compounds in the red yeast rice fermented with Monascus spp. have the anti-diabetic effects and what their pharmacological mechanism is.